OSCR

Dissecting acute neuronal responses to glioblastoma using a dual-interface human iPSC neuronal culture platform.

Overview

Authors: Ouada Nebie1,2, Niyi Adelakun1,2,3, Brian Fries4, Luke Kollin5, Liwen Zhang4, Akhil Medikonda1, Monica Venere5, Pierre Giglio6,7, Nam Chu1,2,3, Nhat Le1,2
  1. Department of Cancer Biology and Genetics, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210 USA
  2. Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH 43210 USA
  3. The Ohio State Biochemistry Program (OSBP), The Ohio State University, Columbus, OH 43210 USA
  4. Campus Chemical Instrument Center, Mass Spectrometry and Proteomics, The Ohio State University, Columbus, OH 43210 USA
  5. Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210 USA
  6. Department of Neurology, College of Medicine, The Ohio State University Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH 43210 USA
  7. Solove Research Institute Comprehensive Cancer Center, College of Medicine, James Cancer Hospital, The Ohio State University Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH 43210 USA
Journal: Acta neuropathologica communications, volume 14, issue 1, article 149
Dates: received 8 January 2026; accepted 24 April 2026; published online 16 May 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1186/s40478-026-02312-z · PMID 42141486 · PMCID PMC13371652 · OpenAlex W7161258329
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: human (organism), other condition (population), cellular / molecular (subfield)
Methods: Statistics
Keywords: Glioblastoma, iPSC-derived neurons, Tumor-neuron interaction, MAPK signaling, ERK1/2, p38α MAPK, Synaptic remodeling, Patient-derived glioblastoma cells
MeSH: Brain Neoplasms*, Glioblastoma*, Induced Pluripotent Stem Cells*, Neurons*, Cell Line, Tumor, Humans, Signal Transduction (* major topic)
Topic: Glioma Diagnosis and Treatment (Genetics, Medicine), according to OpenAlex
Funding: NCI NIH HHS (R01 CA280203, R21 CA271217, K22 CA241105, P30 CA016058); National Cancer Institute; National Institute of General Medical Sciences; The Daniel J. Zwayer Brain Cancer Research Fund; Warren Alpert Foundation; NIGMS NIH HHS (R35 GM151124)
Citations: not cited yet (Europe PMC); 41 references in the paper
Research resources: The Ohio State University RRID:SCR_025078

Abstract

Glioblastoma (GB) hijacks neuronal circuits to promote tumor progression, but the earliest neuronal responses remain poorly defined. We developed a dual-interface human iPSC-derived neuronal model to study acute paracrine signaling triggered by GB cells from two sources: serum-adapted U-87MG and serum-free NU-757. Within 24 h, exposed neurons displayed synaptic remodeling and activation of GB-related signaling cascades. Neurons exposed to U-87MG showed decreased dendritic spine number alongside increased total ERK and phospho-p38α at spines (1). In the soma, total ERK accumulated in the nucleus while phospho-ERK was primarily cytoplasmic; nuclear p38 and cytoplasmic MLK2 also increased (2). Conversely, NU-757 exposure enhanced spine growth but reduced postsynaptic density, NMDAR, and synaptophysin levels (3). Both total and phospho-ERK showed increased nuclear localization with NU-757, while total MLK2 and p38α levels remained stable but exhibited elevated nuclear (4) and spine localization. Pharmacological MEK/ERK inhibition reduced U-87MG proliferation and migration and restored neuronal spine numbers. This model system reveals source-dependent, compartment-specific signaling dynamics that govern synaptic vulnerability and provides a platform for investigating GB initiation, recurrence, and progression, as well as therapies targeting tumor growth and neural circuit remodeling.

Supplementary Information: The online version contains supplementary material available at 10.1186/s40478-026-02312-z.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none, so it has no map.

Data

Datasets cited

Data availability

No datasets were generated or analysed during the current study.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 10 authors, 8 keywords, 7 MeSH terms, 6 funders, 40 references, 1 RRID.

Cite

This paper

Nebie, O., Adelakun, N., Fries, B., Kollin, L., Zhang, L., Medikonda, A., Venere, M., Giglio, P., Chu, N., & Le, N. (2026). Dissecting acute neuronal responses to glioblastoma using a dual-interface human iPSC neuronal culture platform. Acta neuropathologica communications, 14(1), 149. https://doi.org/10.1186/s40478-026-02312-z

BibTeX

@article{nebie2026dissecting,
author = {Nebie, Ouada and Adelakun, Niyi and Fries, Brian and Kollin, Luke and Zhang, Liwen and Medikonda, Akhil and Venere, Monica and Giglio, Pierre and Chu, Nam and Le, Nhat},
title = {{Dissecting acute neuronal responses to glioblastoma using a dual-interface human iPSC neuronal culture platform}},
journal = {Acta neuropathologica communications},
year = {2026},
month = may,
volume = {14},
number = {1},
pages = {149},
publisher = {BMC},
issn = {2051-5960},
doi = {10.1186/s40478-026-02312-z},
url = {https://doi.org/10.1186/s40478-026-02312-z},
pmid = {42141486},
pmcid = {PMC13371652}
}

RIS

TY - JOUR
AU - Nebie, Ouada
AU - Adelakun, Niyi
AU - Fries, Brian
AU - Kollin, Luke
AU - Zhang, Liwen
AU - Medikonda, Akhil
AU - Venere, Monica
AU - Giglio, Pierre
AU - Chu, Nam
AU - Le, Nhat
TI - Dissecting acute neuronal responses to glioblastoma using a dual-interface human iPSC neuronal culture platform
T2 - Acta neuropathologica communications
J2 - Acta Neuropathol Commun
PY - 2026
DA - 2026/05/16
VL - 14
IS - 1
SP - 149
SN - 2051-5960
PB - BMC
DO - 10.1186/s40478-026-02312-z
UR - https://doi.org/10.1186/s40478-026-02312-z
LA - en
ER -

CSL-JSON

{
"id": "10.1186/s40478-026-02312-z",
"type": "article-journal",
"title": "Dissecting acute neuronal responses to glioblastoma using a dual-interface human iPSC neuronal culture platform",
"container-title": "Acta neuropathologica communications",
"author": [
{
"family": "Nebie",
"given": "Ouada"
},
{
"family": "Adelakun",
"given": "Niyi"
},
{
"family": "Fries",
"given": "Brian"
},
{
"family": "Kollin",
"given": "Luke"
},
{
"family": "Zhang",
"given": "Liwen"
},
{
"family": "Medikonda",
"given": "Akhil"
},
{
"family": "Venere",
"given": "Monica"
},
{
"family": "Giglio",
"given": "Pierre"
},
{
"family": "Chu",
"given": "Nam"
},
{
"family": "Le",
"given": "Nhat"
}
],
"container-title-short": "Acta Neuropathol Commun",
"volume": "14",
"issue": "1",
"page": "149",
"DOI": "10.1186/s40478-026-02312-z",
"PMID": "42141486",
"PMCID": "PMC13371652",
"ISSN": "2051-5960",
"publisher": "BMC",
"URL": "https://doi.org/10.1186/s40478-026-02312-z",
"language": "en",
"issued": {
"date-parts": [
[
2026,
5,
16
]
]
}
}

Similar papers

The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.

[1] doi:10.1093/neuonc/noag059
Combined patch-clamp electrophysiology and single-cell genomic analysis reveal spiking tumor cells at the neocortical glioblastoma interface in humans.
Journal: Neuro-oncology
In common: other condition, cellular / molecular, 6 references
[2] doi:10.1038/s41467-026-76587-0 [code]
Uncovering the signaling networks of disseminated glioblastoma cells in vivo with INSIGHT.
Journal: Nature communications
In common: other condition, cellular / molecular, 6 references
[3] doi:10.3390/ijms27104300
A Synaptogenesis-Associated Histomorphologic Signature from H&E Whole-Slide Images Predicts Glioma Prognosis and Identifies <i>EFNB2</i>-Positive Malignant Cells as a Candidate Neuro-Glioma Communication Hub.
Journal: International journal of molecular sciences
In common: other condition, 5 references
[4] doi:10.1038/s41586-026-10631-3 [code]
A prognostic human brain network for diffuse midline glioma.
Journal: Nature
In common: other condition, 4 references
[5] doi:10.1186/s12967-026-08266-z [code]
Single-cell multi-omic integration analysis prioritizes druggable genes and reveals cell-type-specific causal effects in glioblastomagenesis.
Journal: Journal of translational medicine
In common: other condition, cellular / molecular, 3 references
[6] doi:10.1038/s41467-026-73726-5
Brain FGF2 and NCAM1 contribute to FGFR1-dependent progression of estrogen receptor-positive breast cancer brain metastases.
Journal: Nature communications
In common: other condition, cellular / molecular, 3 references
[7] doi:10.3389/fncel.2026.1713437 [code]
Single-nucleus transcriptomics identifies cell cycle and synaptic pathway dysregulation during OPC-to-glioma progression.
Journal: Frontiers in cellular neuroscience
In common: other condition, cellular / molecular, 3 references
[8] doi:10.3389/fimmu.2026.1824726
Glioma-intrinsic SLC1A3 hijacks the vascular niche to establish an immunosuppressive microenvironment.
Journal: Frontiers in immunology
In common: other condition, cellular / molecular, 2 references
[9] doi:10.1002/adhm.202504842
Flash Assembloids: A Rapid Biofabrication of a Platform for Modeling Early Glioblastoma Invasion at the Glioblastoma-Brain Organoid Interfaces.
Journal: Advanced healthcare materials
In common: other condition, 2 references
[10] doi:10.1016/j.xcrm.2026.102766 [code]
A longitudinal single-cell and spatial multiomic atlas of pediatric high-grade glioma.
Journal: Cell reports. Medicine
In common: other condition, cellular / molecular, 2 references

Contribute

The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.

Sign in with ORCID to claim this paper as one of its authors, correct its record or validate its tracing map: when the paper's metadata lists your ORCID iD, you are recognized at once. Maintainers of its code: sign in with GitHub, then claim the repository on your account page.

Request its removal

To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).

Discussion, reproductions, activity

Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.

Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.

Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.